Abstract

Background

Macrophages and fibroblasts are two major players in tissue repair and fibrosis. Despite
the relevance of macrophages and fibroblasts in tissue homeostasis, remarkably little
is known whether macrophages are able to influence the properties of fibroblasts.
Here we investigated the role of paracrine factors secreted by classically activated
(M1) and alternatively activated (M2) human macrophages on human dermal fibroblasts
(HDFs).

Results

HDFs stimulated with paracrine factors from M1 macrophages showed a 10 to > 100-fold
increase in the expression of the inflammatory cytokines IL6, CCL2 and CCL7 and the
matrix metalloproteinases MMP1 and MMP3. This indicates that factors produced by M1
macrophages induce a fibroblast phenotype with pro-inflammatory and extracellular
matrix (ECM) degrading properties. HDFs stimulated with paracrine factors secreted
by M2 macrophages displayed an increased proliferation rate. Interestingly, the M1-activated
pro-inflammatory fibroblasts downregulated, after exposure to paracrine factors produced
by M2 macrophages or non-conditioned media, the inflammatory markers as well as MMPs
and upregulated their collagen production.

Conclusions

Paracrine factors of M1 or M2 polarized macrophages induced different phenotypes of
HDFs and the HDF phenotypes can in turn be reversed, pointing to a high dynamic plasticity
of fibroblasts in the different phases of tissue repair.